Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial.

Abstract

BACKGROUND:

The 2013-2016 Ebola virus outbreak in West Africa was the most widespread in history. In response, alive attenuated recombinant vesicular stomatitis virus (rVSV) vaccine expressing Zaire Ebolavirus glycoprotein (rVSVΔG-ZEBOV-GP) was evaluated in humans.

METHODS:

In a phase 1, randomized, dose-ranging, observer-blind, placebo-controlled trial, healthy adults aged 18-65 years were randomized into 4 groups of 10 to receive one of 3 vaccine doses or placebo. Follow-up visits spanned 180 days postvaccination for safety monitoring, immunogenicity testing and any rVSV virus shedding.

RESULTS:

Forty participants were injected with rVSVΔG-ZEBOV-GP vaccine (n = 30) or saline placebo (n = 10). No serious adverse events related to the vaccine or participant withdrawals were reported. Solicited adverse events during the 14-day follow-up period were mild to moderate and self-limited, with the exception of injection-site pain and headache. Viremia following vaccination was transient and no longer detectable after study day 3, with no virus shedding in saliva or urine. All vaccinated participants developed serum immunoglobulin G (IgG), as measured by Ebola virus envelope glycoprotein-based enzyme-linked immunosorbent assay (ELISA). Immunogenicity was comparable across all dose groups, and sustained IgG titers were detectable through to the last visit, at study day 180.

INTERPRETATION:

In this phase 1 study, there were no safety concerns after a single dose of rVSVΔG-ZEBOV-GP vaccine. IgG ELISA showed persistent high titers at 180 days postimmunization. There was a period of reactogenicity, but in general, the vaccine was well tolerated. This study provides evidence of the safety and immunogenicity of rVSVΔG-ZEBOV-GP vaccine and importance of its further investigation. Trial registration: Clinical-Trials.gov no., NCT02374385.

• Authors: May S ElSherif, Catherine Brown, Donna MacKinnon-Cameron, Li Li, Trina Racine, Judie Alimonti, Thomas L Rudge, Carol Sabourin, Peter Silvera, Jay W Hooper, Steven A Kwilas, Nicole Kilgore, Christopher Badorrek, W Jay Ramsey, D Gray Heppner, Tracy Kemp, Thomas P Monath, Teresa Nowak, Shelly A McNeil, Joanne M Langley, Scott A Halperin, Canadian Immunization Research Network
• Journal: CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne (CMAJ) Vol. 189 Issue 24 Pg. E819-E827 (Jun 19 2017) ISSN: 1488-2329 [Electronic] Canada
• PMID: 28630358 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial)
• Copyright: © 2017 Canadian Medical Association or its licensors.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Ebola Vaccines
• G protein, vesicular stomatitis virus
• Immunoglobulin G
• Membrane Glycoproteins
• Vaccines, Synthetic
• Viral Envelope Proteins

Topics

• Adolescent
• Adult
• Animals
• Antibodies, Neutralizing (blood)
• Antibodies, Viral (blood)
• Canada
• Double-Blind Method
• Ebola Vaccines (administration & dosage)
• Ebolavirus
• Female
• Healthy Volunteers
• Hemorrhagic Fever, Ebola (prevention & control)
• Humans
• Immunoglobulin G (blood)
• Male
• Membrane Glycoproteins (genetics, immunology)
• Middle Aged
• Regression Analysis
• Vaccination (methods)
• Vaccines, Synthetic (administration & dosage)
• Vesicular stomatitis Indiana virus
• Viral Envelope Proteins (genetics, immunology)
• Young Adult